Researchers at MIT and other institutions have created tiny
freeze-dried pellets that include all of the molecular machinery needed to
translate DNA into proteins, which could form the basis for on-demand
production of drugs and vaccines. Image: Christine Daniloff/MIT.
Antimicrobial peptide illustration by Ymahn/Wikimedia Commons.

Freeze-dried cellular components can be re-hydrated to churn out
useful proteins

Anne Trafton, MIT News Office, September 22,
2016: Researchers at MIT and other institutions have created tiny
freeze-dried pellets that include all of the molecular machinery needed
to translate DNA into proteins, which could form the basis for on-demand
production of drugs and vaccines.

The pellets, which contain
dozens of enzymes and other molecules extracted from cells, can be
stored for an extended period of time at room temperature. Upon the
addition of water and freeze-dried DNA, the pellets begin producing
proteins encoded by the DNA.

“It’s a modular system that can be
programmed to make what you need, on the spot,” says James Collins, the
Termeer Professor of Medical Engineering and Science in MIT’s Department
of Biological Engineering and Institute for Medical Engineering and
Science (IMES). “You could have hundreds of different DNA pellets you
can add in the field. These pellets, a few millimeters in diameter,
could be easily carried by soldiers, astronauts, or health care workers
heading to remote areas,” says Collins, who is the senior author of a
paper describing this strategy in the Sept. 22 online edition of Cell.

The paper’s lead authors are Keith Pardee, an assistant professor at
the University of Toronto and former research scientist at Harvard
University’s Wyss Institute for Biologically Inspired Engineering;
Shimyn Slomovic, an IMES postdoc; Jeong Wook Lee, a Wyss Institute
research scientist; and Peter Nguyen, a Wyss Institute Technology
Fellow.

Cell-free synthesis
Collins and many others in the growing field of synthetic biology have
previously designed cells to perform many functions they don’t normally
have, such as producing drugs or bio-fuels. Over the past few years,
Collins has shown that this kind of design can also be done outside of
cells, by extracting the necessary cellular components and freeze-drying
them onto paper or other materials.

“The cell-free extracts
consist of a few dozen enzymes, DNA, and RNA, as well as ribosomes and
other molecular machines leading to transcription and translation,”
Collins says.In the new study, the researchers took the paper out of
the equation: The cellular extracts are simply freeze-dried into
pellets, which remain stable for at least a year. To activate protein
production, the researchers add water to re-hydrate the pellets, along
with freeze-dried DNA that encodes the desired protein.

This
approach could be useful for generating a wide range of products,
including both drugs and molecules that could be used to diagnose
illness. In the Cell study, the researchers produced small proteins that
could be used as a diphtheria vaccine, as well as antimicrobial
peptides, which hold potential to fight bacterial infections.

They also programmed the pellets to generate enzymes that form a
multi-step metabolic pathway that synthesizes a complex drug known as
violacein, which has anticancer and antibiotic activity. For diagnostic
applications, the researchers used the pellets to produce several
different types of antibodies, including one that can detect the
bacterium Clostridium difficile, which can produce severe inflammation
of the colon.

Easy storageThis approach
could prove easier than using live cells to generate bio-pharmaceuticals
because the freeze-dried components are easy to store and ship, and they
don’t need to be refrigerated.

“Collins and colleagues paint a
future where freeze-dried, cell-free bio-manufacturing platforms can be
used to synthesize therapeutics, vaccines, and biochemicals on demand,
without the need for a cold [supply] chain,” says Michael Jewett, an
associate professor of chemical and biological engineering at
Northwestern University, who was not involved in the research. “By
moving manufacturing from the factory to the front lines, we might be
able to provide patient-specific medicines where medicines are not
available now.”

Collins anticipates that this type of technology
should be useful in a variety of settings.“It could be used in a
very simple carry kit for health care workers going in the field in
developing regions,” he says. “We think it could be very useful for the
military, when you’re going out on a mission in the field, or for hikers
and athletes going for long hauls. You could even have it in the back of
your car as an expanded first aid kit.”

These pellets could also
be incorporated into educational tools – “the biotech equivalent of a
chemistry kit,” Collins says. “You could envision using these pellets to
allow students to conduct synthetic biology experiments at home, or in
middle schools and high schools.”

Another application Collins
plans to pursue is integrating the pellets into “smart bandages” that
would detect an infection and then begin producing the appropriate
antimicrobial peptide to treat the infection.

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